West Midlands Police said they were called just after 8.30pm on Sunday to the incident on Dulwich Road in Kingstanding.
One house has been destroyed and several others have been significantly damaged as well as nearby cars, the force said.
West Midlands Ambulance Service (WMAS) said people at the scene rescued a man from the destroyed house but he had "very significant injuries" and was taken to hospital.
Residents described to the PA news agency how they clambered past flaming debris, through dust and rubble, shortly after the blast, and pulled an injured man alive from the ruins of the house.
One man, who declined to give his name, said: "Everyone was watching, the house was on fire, nobody was going in, so we could see a way in - so we went in the house, me and about a dozen others.
"There was a guy in the back (of the house), we could hear the guy screaming, but he was trapped up against the fridge in the kitchen.
"The dust from the loft insulation was burning around us.
"We managed to get to him, and pull him out - I still have his blood on my jeans.
"We got him out, he ended up coming out on a mattress.
"But he was saying there was a woman in the house."
Four other men suffered minor injuries and were assessed by ambulance crews at the scene, WMAS added.
A spokesperson said: "A man was helped from the property by people at the scene but had suffered very serious injuries.
"After assessment and treatment at the scene, he was taken on blue lights to the major trauma centre at Queen Elizabeth Hospital Birmingham with the MERIT team travelling with the ambulance.
"His condition on arrival at hospital was described as life threatening.
"Four further men have been assessed by ambulance crews for minor conditions but have been discharged at the scene.
"Members of the Hazardous Area Response Team continue to work with specialist firefighters at the scene."
A spokesperson from Cadent Gas said its personnel were at the site.
"Our teams are on-site at the incident in Kingstanding, assisting the multi-agency response as the gas emergency service for the West Midlands" they said.
"It is too early to speculate on the cause. Our thoughts are with everyone impacted.
"If ever anyone smells gas, nearby or anywhere, it is important to act immediately and ring the national gas emergency service on 0800 111 999."
Footage on social media showed flames, damage and debris from a terraced red brick house.
Aerial shots shared on Twitter also showed flames billowing into the sky.
Emergency services said evacuations were taking place and people have been urged to avoid the area, with Dulwich Road and surrounding roads closed.
Emergency services said the cause of the fire is not yet known.
WMFS said it was working with West Midlands Police, WMAS, Cadent Gas and the National Grid were all working to manage the incident.
Six fire crews, three ambulances, five paramedic officers and a National Inter-Agency Liaison officer were among the resources sent to the scene.
Rick Payne, a city councillor for the ward, heard a "massive explosion" while watching television shortly after 8.30pm, and walked across to Dulwich Road to see what had happened.
He said: "I recognised that as probably most likely to be a gas explosion.
"The police are just saying that there's quite a lot of houses damaged as a result - probably up to five or six houses.
"The house itself, where the explosion occurred, has physically been destroyed. Houses either side have, partially. Then the houses further along the street have been damaged collaterally from the blast."
A man "put his own life at risk" by running into a burning house to save someone inside after the explosion, according to his cousin.
Callum Attwood's cousin Reece wrote on Twitter: "What happened in Kingstanding tonight is devastating... my cousin saved a life! He's a hero. I'm so proud of him.
"Get this spread round Twitter!! His actions, Braveness and courage to do what someone else wouldn't do and put his own life at risk to save a life! Hero CALLUM ATTWOOD."
WMFS area commander Steve Ball, speaking at the scene, said: "Around 8.30pm this evening we were called to a gas explosion in a house.
"On arrival, it was quite a challenging scene, where one house had been completely destroyed, and three neighbouring properties had also been quite badly affected.
"One man had already been rescued, prior to our arrival, and he's been taken care of by West Midlands Ambulance Service.
"He's got life-threatening injuries and he's gone to the Queen Elizabeth Hospital (Birmingham).
"On scene at the moment we've got six appliances, we've got our technical rescue teams and we've also got our fire dog here."